Reagent for inhibiting osteoclast activity and treating osteoporosis and application thereof
A technology for osteoporosis and osteoclasts, which can be used in bone diseases, biological testing, peptide/protein components, etc., and can solve problems such as lack of drug treatment and bone loss.
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Embodiment 1
[0227] Example 1. Deletion of Piezo1 in osteoblast cells leads to severe osteoporosis
[0228] As mechanosensitive channels, PIEZO family can transduce mechanical stimuli in various tissues and organs, and previous research results imply its role in osteogenesis.
[0229] In order to study the role of this family in bone cells, the inventors first detected the expression abundance of its two members, Piezo1 and Piezo2, in bone, osteoblasts and osteoclasts, and found that Piezo2 is mainly expressed in dorsal root neurons expression, while Piezo1 was more highly expressed in bone, osteoblasts and osteoclasts ( figure 1 A-C), indicating that Piezo1 may play a major role in the skeletal system. In order to further study the influence of Piezo1 on the skeletal system, the inventors constructed a conditional knockout mouse of Piezo1, that is, using Prx1 Cre Specifically knocking out Piezo1 in mesoderm-derived mesenchymal stem cells ( figure 1 D-E). Prx1 Cre Expressed in extremi...
Embodiment 2
[0234] Example 2. Deletion of Piezo1 in osteoblast cells leads to enhanced activity of osteoclasts
[0235] Osteoporosis is generally caused by abnormal bone remodeling, that is, an imbalance between bone formation and bone resorption. Osteoblasts are derived from skeletal stem cells (skeletal stem cells, SSCs; CD31-CD45-Ter119-CD90-6C3-CD105-CD200+), osteochondral and stromal progenitor cells (pre-bone, cartilage and stroma progenitors, pre- BCSPs, CD31-CD45-Ter119-CD90-6C3-CD105-CD200-) and osteochondral stromal progenitors (bone, cartilage and stromal progenitors, BCSPs, CD31-CD45-Ter119-CD90-6C3-CD105+), their lineage maintenance and Differentiation is strictly regulated. The inventors therefore isolated WT and Prx1 Cre ;Piezo1 fl / fl In mouse bone marrow cells, it was found that the loss of Piezo1 had no significant effect on the number of skeletal stem cells, progenitor cells and precursor cells by flow cytometry analysis ( Figure 5 A-B). The present inventors specu...
Embodiment 3
[0237] Example 3, PIEZO1 can feel the mechanical stress stimulus caused by load bearing
[0238] According to the foregoing, deletion of the Piezo1 gene in osteoblastic lineage cells resulted in enhanced osteoclast activity in long bones, but had no significant effect on osteoclast activity in cranial parietal bones ( Figure 7 A); Simultaneously on nascent day 0 WT and Prx1 Cre ;Piezo1 fl / fl Compared with the osteoclast activity of mice, there was no significant change ( Figure 7 B and D); but Prx1 after 3 days of birth Cre ;Piezo1 fl / fl The osteoclast activity of mice was significantly enhanced ( Figure 7 C and E). These results suggest that the enhancement of osteoclast activity by Piezo1 deletion in osteoblasts is dependent on postnatal bodyweight-induced changes in mouse bone response to mechanical stimuli.
[0239] In order to further explore whether PIEZO1 can play a role in mechanical stimulus sensing in osteoblast lineage cells, the inventors used a hindlimb s...
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Abstract
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